Celecoxib (Celebrex)

1. Health Canada Product Monograph — Celecoxib

• Celecoxib relieves the symptoms of osteoarthritis.
• Celecoxib relieves the symptoms of adult rheumatoid arthritis.
• Celecoxib relieves the symptoms of ankylosing spondylitis.
• Celecoxib is used for short-term (up to 7 days) management of moderate to severe acute pain, such as after musculoskeletal injury, orthopedic surgery, or dental extraction.
• Celecoxib relieves symptoms and reduces inflammation but does not treat the underlying disease or stop its progression.

Contraindicated in pregnancy. Confirm pregnancy status and discuss alternative therapy with the prescriber before dispensing.

• Celecoxib is contraindicated in the third trimester of pregnancy due to the risk of premature closure of a blood vessel in the baby's heart (the ductus arteriosus) and prolonged labour.
• Caution is recommended when prescribing celecoxib during the first and second trimesters of pregnancy.
• Use from around 20 weeks of pregnancy onward may cause reduced amniotic fluid (oligohydramnios) and kidney problems in the baby, sometimes occurring within 2 days of starting treatment.
• If celecoxib must be used between roughly 20 weeks and the end of the second trimester, the lowest effective dose should be used for the shortest possible time, with ultrasound monitoring of amniotic fluid considered if treatment continues beyond 48 hours.
• NSAID use in early pregnancy has been associated with an increased risk of miscarriage and heart defects in epidemiological studies.

• Celecoxib is contraindicated in women who are breastfeeding because of the potential for serious reactions in the nursing infant.

• Older adults and frail or debilitated patients are more likely to experience adverse reactions from celecoxib, and the risk increases with dose and duration of treatment.
• Older adults are less able to tolerate stomach ulceration and bleeding, and most reports of fatal gastrointestinal events occur in this age group.
• A lower starting dose should be considered in older, frail, or debilitated patients, with individual adjustment as needed.

• Celecoxib is contraindicated in children and adolescents under 18 years of age because safety and efficacy have not been established in this population.

• For osteoarthritis, the usual dose is 200 mg daily, taken as a single dose or split into two doses of 100 mg.
• For rheumatoid arthritis, the starting dose is 100 mg twice daily, which may be increased to 200 mg twice daily if needed.
• For ankylosing spondylitis, the usual dose is 200 mg daily, taken as a single dose or split into two doses of 100 mg.
• For acute pain, the usual dose is 400 mg as a single dose on the first day, followed by 200 mg once daily on subsequent days, for up to 7 days.
• In patients with mild liver impairment, celecoxib should be started at the lowest dose; in moderate liver impairment, the daily dose should be reduced by half, to a maximum of 100 mg once daily.
• No dose adjustment is needed for mild kidney impairment (creatinine clearance above 30 mL/min).
• In frail or elderly patients, the lowest effective dose should be used.
• Patients who are known or suspected to be poor metabolizers of the CYP2C9 enzyme should start at half the usual lowest dose, with a maximum of 100 mg daily.
• The lowest effective dose should always be used for the shortest duration needed to control symptoms.
• If a dose is missed, the next dose should be taken at the regular scheduled time; the dose should not be doubled.

If overdose is suspected, seek emergency medical attention immediately or contact your regional Poison Control Centre without delay.

• No serious toxicity has occurred in reported cases of celecoxib overdose, even at doses up to 2400 mg per day for up to 10 days.
• Symptoms of NSAID overdose typically include lethargy, drowsiness, nausea, vomiting, and stomach pain, and are usually reversible with supportive care.
• Gastrointestinal bleeding, high blood pressure, acute kidney failure, slowed breathing, and coma may occur but are rare.
• There is no specific antidote for celecoxib overdose; treatment is symptomatic and supportive.
• Activated charcoal may be given if the patient is seen within 4 hours of a large overdose.
• Because celecoxib binds strongly to blood proteins, dialysis is not expected to be useful in removing it from the body.

• Headache may occur.
• Diarrhea may occur.
• Indigestion (dyspepsia) may occur.
• Abdominal pain may occur.
• Nausea may occur.
• Gas (flatulence) may occur.
• Dizziness may occur.
• Swelling in the legs or ankles (peripheral edema) may occur.
• Sinusitis or upper respiratory tract infection symptoms may occur.
• Insomnia may occur.
• Back pain may occur.
• Skin rash may occur.

Serious side effects require immediate discussion with the prescriber or emergency care.

• Celecoxib increases the risk of serious cardiovascular events such as heart attack and stroke, which can be fatal, and this risk increases with higher doses and longer use.
• Serious gastrointestinal problems including stomach or intestinal ulcers, bleeding, and perforation can occur at any time, with or without warning symptoms.
• Severe liver reactions, including liver failure and hepatitis, have been reported, sometimes fatal.
• Severe skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS), have occurred, usually within the first month of treatment.
• Serious allergic (anaphylactic) reactions can occur, even in patients with no known prior exposure to celecoxib.
• Kidney problems, including acute kidney failure, can occur, especially in patients who are dehydrated or have pre-existing kidney disease.
• Blood disorders such as low platelet counts, low white blood cell counts, or aplastic anemia have rarely been reported.
• Fluid retention and worsening of congestive heart failure can occur.
• New or worsening high blood pressure can occur.
• Aseptic meningitis, with fever, stiff neck, and headache, has rarely been reported, particularly in patients with autoimmune disorders such as lupus.
• Seek urgent medical attention for chest pain, sudden weakness or slurred speech, black or bloody stools, severe stomach pain, yellowing of the skin or eyes, or a severe skin rash.

• Use with caution in patients with risk factors for cardiovascular disease, such as high blood pressure, high cholesterol, diabetes, or smoking.
• Use with caution in patients with a history of stomach ulcers or gastrointestinal bleeding, who have a much higher risk of a GI bleed while taking an NSAID.
• Use with caution in patients taking anticoagulants such as warfarin, as the combination increases bleeding risk.
• Use with caution in patients with reduced kidney function or conditions predisposing to dehydration.
• Use with caution in patients with a history of asthma, nasal polyps, or allergic-type reactions to aspirin or other NSAIDs.
• Use with caution in frail, elderly, or debilitated patients, who tolerate side effects less well.
• Use with caution in patients trying to become pregnant, as celecoxib may reduce fertility.
• Use with caution in patients on long-term therapy, who should have periodic monitoring of blood counts, liver function, and kidney function if signs of a problem develop.

• Contraindicated in patients with known hypersensitivity to celecoxib or any ingredient in the formulation.
• Contraindicated in patients with a known allergy to sulfonamide medications.
• Contraindicated in patients with a history of asthma, hives, or allergic-type reactions after taking aspirin or other NSAIDs.
• Contraindicated in patients with active stomach or duodenal ulcers or active gastrointestinal bleeding.
• Contraindicated in patients with inflammatory bowel disease.
• Contraindicated in patients with severe liver impairment or active liver disease.
• Contraindicated in patients with severe kidney impairment or deteriorating kidney disease.
• Contraindicated in patients with severe, uncontrolled heart failure.
• Contraindicated in patients with a history of bleeding in the brain (cerebrovascular bleeding).
• Contraindicated in patients with known high blood potassium (hyperkalemia).
• Contraindicated for use around the time of coronary artery bypass graft (CABG) surgery.
• Contraindicated during the third trimester of pregnancy.
• Contraindicated in women who are breastfeeding.
• Contraindicated in children and adolescents under 18 years of age.

• Combining celecoxib with other NSAIDs, including over-the-counter products like ibuprofen, is not recommended because of the added risk of side effects without added benefit.
• Combining celecoxib with anticoagulants such as warfarin increases the risk of serious, sometimes fatal, bleeding, and requires close monitoring.
• Combining celecoxib with low-dose aspirin increases the risk of stomach ulcers and gastrointestinal bleeding compared with celecoxib alone.
• Fluconazole roughly doubles celecoxib blood levels by blocking its breakdown, so a lower celecoxib dose is recommended when used together.
• Aluminum- and magnesium-containing antacids can reduce celecoxib absorption; concomitant use is not recommended.
• Celecoxib may reduce the blood-pressure-lowering effects of ACE inhibitors, angiotensin receptor blockers, diuretics, and beta-blockers.
• Combining celecoxib with ACE inhibitors, angiotensin receptor blockers, or diuretics can increase the risk of kidney problems, especially in older or dehydrated patients.
• Celecoxib increases blood levels of drugs broken down by the CYP2D6 enzyme, such as dextromethorphan and metoprolol, potentially requiring a dose adjustment of those drugs.
• Combining celecoxib with oral corticosteroids increases the risk of stomach ulcers and bleeding.
• Combining celecoxib with SSRIs, such as citalopram, paroxetine, fluoxetine, or sertraline, increases the risk of gastrointestinal bleeding.
• Celecoxib may increase lithium blood levels, requiring monitoring when starting or stopping celecoxib.
• Combining celecoxib with methotrexate may increase the risk of methotrexate toxicity.
• Combining celecoxib with cyclosporine or tacrolimus may increase the risk of kidney toxicity.

• Celecoxib can be taken with or without food.

• Celecoxib can be taken at any time of day, with or without food, according to individual preference and dosing schedule.

• Store celecoxib capsules at room temperature (15°C to 30°C).

• Use the lowest effective dose for the shortest time needed to control your symptoms.
• Celecoxib relieves symptoms of arthritis and pain but does not cure the underlying condition.
• Seek immediate medical attention for chest pain, sudden weakness, severe stomach pain, black or bloody stools, or a severe skin rash.
• Tell your doctor about all heart, kidney, liver, or stomach problems before starting celecoxib, and avoid combining it with other NSAIDs unless directed.